The prevalence of obesity and noninsulin-dependent diabetes mellitus (NIDDM) is relatively high in Mexican Americans. Substantial evidence, including the high degree of familial aggregation in NIDDM and measures of fat accumulation, indicates that these traits are influenced by genes. Moreover, such genes may indirectly contribute to the overall risk of cardiovascular disease by influencing a variety of atherosclerosis-related traits. The overall goals of this project are: (1) to detect and localize the genes which influence susceptibility to obesity and NIDDM, and (2) to identify the pleiotropic effects of these genes on lipoproteins, measures of carotid wall thickness, and fibrinolysis phenotypes. Data will be analyzed from approximately 1,400 individuals in more than 40 different families who were enrolled in the San Antonio Family Heart Study during the initial funding period of this grant. The obesity, NIDDM, and lipoprotein phenotypes were characterized at the baseline examination, and measures of carotid wall thickness and fibrinolysis will be obtained by Core A on a set of 750 participants in a recall examination. A set of 391 highly polymorphic microsatellite markers will be typed in Project 2 spanning approximately 10 cM distances throughout the entire genome. The foremost priority in Project 3 will be to detect linkage of those NIDDM-and obesity-related traits for which a major gene has been identified in the current grant period (i.e., fat mass, body mass index, bioresistance, 2-hour insulin concentrations, and diabetes age of onset). The results of a linkage screening analysis performed in Project 2 will be used to guide the choice of markers for a more extensive linkage analysis. If initial linkage and combined linkage/segregation analyses provide support for linkage, Project 2 will type additional markers in that region and Project 3 investigators will perform multipoint and disequilibrium analyses to seek more persuasive evidence for linkage and to further localize the genes. If linkage to an obesity or NIDDM phenotype is detected, multivariate linkage analysis will be used to determine whether that marker is also linked to lipoprotein phenotypes, or to measures of carotid wall thickness and fibrinolysis.